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Mutation BioA414 Population Genetics Handout VI Mutation • Heritable changes within DNA – Converts one allelic form of a gene to another – Rate low and varies between loci and between species – Env. Factors chemicals, radiation and infectious agents ↑number of mutations • Source of all new genetic variation • Raw material for evolution Spontaneous mutation frequencies at specific loci for various organisms • Probability likelihood an error will occur + it will be repaired – Synonymous mutation no alteration of the amino acid – Nonsynonymous mutation alteration of the amino acid 1 Spontaneous mutation frequencies at specific loci for various organisms Organism Trait Mutation/100,000 game tes Consider a hypothetical population • p = f(A) and q = f(a) assume large population + no selection • In each g. a proportion u of all A a – Number of mutati ons depends on u and p A pop. of 100,000 A u equals 10 -4 , 1/10,000 A a p = 1.0 10 -4 x 100,000 = 10 p = 0.1 10 -4 x 10,000 = 1 – The decrease in p due to A a = up – The increase in p due to A a = vq – Amount of A ↓ = increase in A (reverse mutations) – decrease in A (forward mutations) Mutation rate varies between loci and among species • ~10-4 to 10-8 mutations/gene/generation • Mutation rate is abbreviated • Some mutations are neutral (no effect on reproductive fitness) • Others are detrimental or lethal (depends on environment) • If population size is large, effects of mutation act slowly Equilibrium frequencies • Forward mutation rate ↑ q and a reverse mutation rate ↓ q • The population achieves equilibrium – Nb of alleles undergoing forward mutation = Nb of alleles undergoing reverse mutation – At this point no change in allelic freq occur – The equilibrium q = … 2 Equilibrium frequencies Equilibrium frequencies • The equilibrium value of p = … • A population initial p = 0.9 and q = 0.1, u =5x10-5 and v = 2x10-5 – Calculate the change in allelic freq in the first generation Irreversible mutation Allele A is fixed (p =1.0) and mutates A a at rate of = 10 -4 Reversible mutation Allele A is fixed (p =1.0) and mutates A a at rate of = 10 -4 ; but allele a mutates a A at a rate of = 10 -5 3 Effective population size • Not all individuals contribute gametes to the next generation • Effective population size (Ne) = equivalent number of adults contributing gametes to the next generation • Ne = (4 x Nf x Nm )/ (Nf + N m ) • If ♂=♀, Ne = N Genetic drift • Island population of 10 individuals 5 with brown eyes (BB) and 5 with green eyes (bb); f(B) = 0.5, f(b) = 0.5 • Typhoon devastates the island 5 people with brown eyes (BB) die • Allelic frequency of b, f(b) = 1.0 • Now imagine the same scenario for an island of 10,000 inhabitants Fixation of a new favorable mutation • May occur rapidly • Selective sweep • Tightly-linked neutral alleles hitchhiking during a selective sweep • Linked regions of DNA around the favorable allele are overrepresented in the population leads to excess of rare alleles at linked loci The fixation or loss of alleles by random genetic drift occurs more rapidly in small populations 4 Sampling occurs naturally The effect of genetic drift is inversely related to population size • Which gametes fertilizes the egg? • What proportion of offspring survive? • What proportion of offspring contribute gametes to the next generation? Large populations = small effe cts A genetic bottleneck Small populations = large e ffe cts A population bottleneck 5 Population bottleneck followed by recovery or extinction Genetic Bottleneck A historical case A severe genetic bottleneck occurred in northern elephant seals European bison/ wisent (Bison bonasus) American bison/ American buffalo (Bison bison) Bison bison faced extinction around the year 1890 Year American bison Before 1492 60,000,000 1890 750 2000 360,000 6 The Island of the Colorblind • Pingelap island in Micronesia pop. has an high (5%) freq. of achromatopsia • Achromatopsia is a rare, autosomal recessive total inability to distinguish colors • A typhoon ↓ island’s population subsequent inbreeding increased the recessive allele responsible for the disease Tristan da Cunha • A remote island in the south Atlantic settled in 1817 by a Scotsman and his family • The current population can trace their ancestry to about two dozen individuals • Genetic structure reflects the distribution of genes that happened to be present in the small group of founders Bottleneck and founder effects • Sampling effects occurs in natural populations – From founder effects a populati on is established by a s mall number of breedi ng indi vi duals – Populati on size remains small / many generations – Subpopul ations are isolated – Chance pl ays a significant role in determining which genes are present among the founders The Founder Effect One ancestor carrie d allele for retinitis pigmentosum Among their 240 de scendents living on the island today, 4 are blind by the disease and 9 othe rs are carrie rs 7 The Dunkers The Dunkers • A religious isolate founded by about 50 families from Germany who settled in Pennsylvania in 1719 • Allele freq. ABO blood group, bent little fingers, hitchhikers thumb differ • These differences founder effect The Founder Effect Old Order Amish populations are deri ved from a few dozen colonists The community is closed Allele and genetic disease frequencies are different from the German ancestral and the surrounding l ocal popul ations 8 Neutral theory of molecular evolution Genetic drift in Drosophila • Genetic drift cause s allele fre quencies to change ove r time Some alleles may go extinct: p 0 – Other alleles may become fixed: p 1 – • • Probability of fixation increases with time Which allele becomes fixed is strictly random – Rare alleles are more likely to be lost (p 0) – Time to fixation/loss varies with Ne and initial allele frequency – Neutral mutations can be used to estimate time elapsed since two populations/species diverged from a common ancestor Balance between mutation and genetic drift • Mutation adds genetic vari ation/genetic drift removes vari ation • Infinite alleles model predicts that mutation and dri ft balance each other to result in a steady state of heterozygosity – Each mutation is assume d to gene rate a novel allele ne ve r obse rve d – Genetic drift ope rates as normal – Hete rozygosity H = (4 Ne )/ (1 + 4 Ne ) – Neutral paramete r = 4 Ne 9 10